Positive association of a Sirt1 variant and parameters of oxidative stress on Alzheimer's disease.

Alzheimer's disease (AD) is a complex neurodegenerative disorder and the most common type of dementia in the elderly. Although its cause is not completely known, several studies suggest that oxidative stress plays an important role in the etiology of this disease. The SIRT1 and SOD2 proteins are linked to pathways that may impair oxidative stress. In this study, we analyzed the association between polymorphisms in these genes and in the APOE gene, through RT-PCR, as well as between environmental factors and the risk of AD. Additionally, the thiobarbituric acid reactive substance assay was performed to estimate the plasma level of malondialdehyde (MDA), a biomarker of lipid peroxidation. Furthermore, some cytogenetic studies indicate that cells of AD patients show increased chromosomal damage; thus, we performed the micronucleus cytome assay to assess cytogenetic damage in AD patients. As expected, the APOE polymorphisms were found to be highly associated with AD. Additionally, the CT genotype of the SIRT1 gene showed a positive association with the disease. The frequencies of genomic damage (micronucleus, buds, nucleoplasmic bridges and binucleated cells), the presence of cell death biomarkers (condensed chromatin, karyorrhexis and pyknosis), and the plasma level of MDA were significantly greater in AD patients than in controls. Our results support the hypothesis that AD is a condition with increased oxidative stress and genomic instability, which may contribute to the neurodegeneration in AD.